Subjektiver Faktor und wissenschaftlich-technische Revolution

UuStB Koeln=38*-910106324 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEManuskriptdr.DEGerman

Priming increases the anti-tumor effect and therapeutic window of 177 Lu-octreotate in nude mice bearing human small intestine neuroendocrine tumor GOT1

Abstract Background 177 Lu-[DOTA 0 , Tyr 3 ]-octreotate ( 177 Lu-octreotate) is used for treatment of patients with somatostatin receptor (SSTR) expressing neuroendocrine tumors. However, complete tumor remission is rarely seen, and optimization of treatment protocols is needed. In vitro studies have shown that irradiation can up-regulate the expression of SSTR1 , 2 and 5 , and increase 177 Lu-octreotate uptake. The aim of the present study was to examine the anti-tumor effect of a 177 Lu-octreotate priming dose followed 24\ua0h later by a second injection of 177 Lu-octreotate compared to a single administration of 177 Lu-octreotate, performed on the human small intestine neuroendocrine tumor cell line, GOT1, transplanted to nude mice. Results Priming resulted in a 1.9 times higher mean absorbed dose to the tumor tissue per administered activity, together with a reduced mean absorbed dose for kidneys. Priming gave the best overall anti-tumor effects. Magnetic resonance imaging showed no statistically significant difference in tumor response between treatment with and without priming. Gene expression analysis demonstrated effects on cell cycle regulation. Biological processes associated with apoptotic cell death were highly affected in the biodistribution and dosimetry study, via differential regulation of, e.g., APOE , BAX , CDKN1A , and GADD45A . Conclusions Priming had the best overall anti-tumor effects and also resulted in an increased therapeutic window. Results indicate that potential biomarkers for tumor regrowth may be found in the p53 or JNK signaling pathways. Priming administration is an interesting optimization strategy for 177 Lu-octreotate therapy of neuroendocrine tumors, and further studies should be performed to determine the mechanisms responsible for the reported effects

Intraoperative transfusion practices in Europe

Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl and increased to 9.8 (1.8) g dl after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7-9 g dl), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold

Intraoperative transfusion practices in Europe

© 2016 The Author. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.Background: Transfusion of allogeneic blood influences outcome after surgery. Despite widespread availability of transfusion guidelines, transfusion practices might vary among physicians, departments, hospitals and countries. Our aim was to determine the amount of packed red blood cells (pRBC) and blood products transfused intraoperatively, and to describe factors determining transfusion throughout Europe. Methods: We did a prospective observational cohort study enrolling 5803 patients in 126 European centres that received at least one pRBC unit intraoperatively, during a continuous three month period in 2013. Results: The overall intraoperative transfusion rate was 1.8%; 59% of transfusions were at least partially initiated as a result of a physiological transfusion trigger- mostly because of hypotension (55.4%) and/or tachycardia (30.7%). Haemoglobin (Hb)- based transfusion trigger alone initiated only 8.5% of transfusions. The Hb concentration [mean (sd)] just before transfusion was 8.1 (1.7) g dl-1 and increased to 9.8 (1.8) g dl-1 after transfusion. The mean number of intraoperatively transfused pRBC units was 2.5 (2.7) units (median 2). Conclusions: Although European Society of Anaesthesiology transfusion guidelines are moderately implemented in Europe with respect to Hb threshold for transfusion (7-9 g dl-1), there is still an urgent need for further educational efforts that focus on the number of pRBC units to be transfused at this threshold

Intraoperative transfusion practices and perioperative outcome in the European elderly: A secondary analysis of the observational ETPOS study

The demographic development suggests a dramatic growth in the number of elderly patients undergoing surgery in Europe. Most red blood cell transfusions (RBCT) are administered to older people, but little is known about perioperative transfusion practices in this population. In this secondary analysis of the prospective observational multicentre European Transfusion Practice and Outcome Study (ETPOS), we specifically evaluated intraoperative transfusion practices and the related outcomes of 3149 patients aged 65 years and older. Enrolled patients underwent elective surgery in 123 European hospitals, received at least one RBCT intraoperatively and were followed up for 30 days maximum. The mean haemoglobin value at the beginning of surgery was 108 (21) g/l, 84 (15) g/l before transfusion and 101 (16) g/l at the end of surgery. A median of 2 [1–2] units of RBCT were administered. Mostly, more than one transfusion trigger was present, with physiological triggers being preeminent. We revealed a descriptive association between each intraoperatively administered RBCT and mortality and discharge respectively, within the first 10 postoperative days but not thereafter. In our unadjusted model the hazard ratio (HR) for mortality was 1.11 (95% CI: 1.08–1.15) and the HR for discharge was 0.78 (95% CI: 0.74–0.83). After adjustment for several variables, such as age, preoperative haemoglobin and blood loss, the HR for mortality was 1.10 (95% CI: 1.05–1.15) and HR for discharge was 0.82 (95% CI: 0.78–0.87). Preoperative anaemia in European elderly surgical patients is undertreated. Various triggers seem to support the decision for RBCT. A closer monitoring of elderly patients receiving intraoperative RBCT for the first 10 postoperative days might be justifiable. Further research on the causal relationship between RBCT and outcomes and on optimal transfusion strategies in the elderly population is warranted. A thorough analysis of different time periods within the first 30 postoperative days is recommended